ABSTRACT: Nonhuman primates are vital research models for understanding human health and disease. Rhesus macaques and marmosets have similar physiology and anatomy to humans, which make them important model systems for NIH-sponsored biomedical research. Specific examples of fields that rely heavily on these nonhuman primates include drug development, cardiovascular studies, infectious disease, cancer immunotherapy and vaccinology. Cell lines for in vitro experiments, as well as ex vivo studies using primary cells, are widely used, and permit nonhuman primate focused researchers to pursue mechanistic studies. In the genomic era the experimental value of such model systems can be greatly expanded if functional genomic tools for altering gene expression are available. Modulation of gene expression permits the use of genetic approaches to answer mechanistic questions underlying biological events. However, for nonhuman primates, as well for all model systems outside of mouse and in vitro human cells, such genetic tools have not existed and this has limited the types of discoveries these fields can produce. The revolutionary CRISPR/Cas9 technology for modulating gene expression is extremely powerful as it i) can create either homozygous null or hypermorphic phenotypes, ii) is highly specific with a very low level of off target events and iii) can be employed in any mammalian primary cells or cell lines. For this proposal we will meet this need and accelerate nonhuman primate researchers? discoveries by creating highly active cutting- edge CRISPR-based functional genomic resource for macaques and marmosets. We chose these two model systems because of their importance for both basic and translational research, as well as the fact that they represent the most widely used nonhuman primate models, with their use promising to increase in importance across multiple fields including neurology, oncology, gerontology and immunology. RELEVANCE TO PUBLIC HEALTH: Nonhuman primates are vital research models for understanding human health and disease. Genetic experiments are a time honored means of making transformative discoveries. However, for nonhuman primates the basic tools for undertaking such genetic studies have not existed and this has limited the types of discoveries regarding human health and disease that these fields can produce. For this proposal we will meet this need and accelerate nonhuman primate researchers? discoveries by creating genetic tools for the macaque and marmoset research community.